Synthesis of 10-Membered Azecines through Pd-Catalyzed Formal [6+4] Cycloaddition and Their Transannular Reaction to Polycyclic Compounds

Azecine fragments are frequently presented in natural products and bioactive compounds. However, minor efforts have been devoted to these 10-membered N-heterocycles, and their synthesis is still challenging. Reported herein is the first catalytic formal [6+4] cycloaddition for the synthesis of 10-membered azecines. Under palladium catalysis, the reaction of delta-vinylvalerolactones and benzofuran-derived azadienes proceeds smoothly to afford benzofuran-fused azecines with high diastereoselectivity in moderate to good yields. A unique transannular reaction of these 10-membered azecines for the construction of polycyclic compounds is also demonstrated. Catalytic formal [6+4] cycloaddition was developed for the synthesis of 10-membered azecines. Under palladium catalysis, the reaction of delta-vinylvalerolactones and benzofuran-derived azadienes proceeds smoothly to afford benzofuran-fused azecines with high diastereoselectivity in moderate to good yields. The unique transformations involving the transannular reaction of these compounds was also demonstrated.image

Automated summary

A catalytic formal [6+4] cycloaddition reaction was developed for the synthesis of 10-membered azecines, which produced benzofuran-fused azecines with high diastereoselectivity in moderate to good yields through the reaction of delta-vinylvalerolactones and benzofuran-derived azadienes under palladium catalysis. The unique transformations involving the transannular reaction of these compounds for the construction of polycyclic compounds were also demonstrated.